A comparison of cytology and fluorescence in situ hybridization for the detection of urothelial carcinoma

PURPOSE: We determine the relative sensitivities of cytology and fluorescence in situ hybridization (FISH) for the detection of urothelial carcinoma. MATERIALS AND METHODS: A mixture of fluorescent labeled probes to the centromeres of chromosomes 3, 7 and 17, and band 9p21 (P16/CDKN2A gene) was used to assess urinary cells for chromosomal abnormalities indicative of malignancy. A total of 280 urine specimens from 265 patients, including 150 with a history of urothelial carcinoma and 115 without a history of urothelial carcinoma, were analyzed. FISH analysis was performed without prior knowledge of clinical findings, that is biopsy, cystoscopy and cytology results. A positive result was defined as 5 or more urinary cells with gains of 2 or more chromosomes. RESULTS: A total of 75 biopsies showed urothelial carcinoma at FISH analysis among the 265 patients. The sensitivity of urine cytology for pTa (36 cases), pTis (18) and pT1-pT4 (15) tumors was 47%, 78% and 60%, respectively, for an overall sensitivity of 58%. The sensitivity of FISH for pTa (37 cases), pTis (17) and pT1-pT4 (19) tumors was 65%, 100% and 95%, respectively, for an overall sensitivity of 81%. FISH was significantly more sensitive than cytology for pTis (p = 0.046), pT1-pT4 (p = 0.025), grade 3 (p = 0.003) and all tumors (p = 0.001). The specificity of cytology and FISH among patients without cystoscopic evidence of urothelial carcinoma and no history of urothelial carcinoma was 98% and 96%, respectively (p = 0.564). CONCLUSIONS: The sensitivity of FISH for the detection of urothelial carcinoma is superior to that of cytology, and the specificity of FISH and cytology for urothelial carcinoma are not significantly different. Further prospective studies are required but FISH has the potential to improve significantly the management of urothelial carcinoma.     

Plasma mineralocorticoids--aldosterone and desoxycorticosterone-- in patients with"low-renin"arterial hypertension

The plasma aldosterone (A) and desoxycorticosterone (DOCS) levels were measured in 10 patients with primary aldosteronism and in 2 subgroups with low-renin hypertensive disease (LRHD): (1) those with normal adrenal glands++ (n - 11) and (2) those with structural changes in the cortex (n - 11). The patients from Subgroup 1 showed the lowest basal A and DOCS levels (107.29 +/- 12.90 and 0.080 +/- 0.013 ng/ml, respectively) and low concentrations of the two hormones after stimulation of 4-hour walk (211.57 +/- 30.47 and 0.095 +/- 0.024 ng/mg, respectively). In the patients from Subgroup 2, the basal and 4-hour post-walk++ A and DOCS contents were increased in the cortex (basal 201.50 +/- 41.59 and 0.177 +/- 0.36 ng/mg and poststimulation 331.33 +/- 30.47 and 0.302 +/- 0.061 ng/ml, respectively). Some patients with primary aldosteronism displayed the same DOCS response to stimulation as did those with LRHD in the presence of structural cortical changes. Histological examination of operative biopsy specimens indicated that higher DOCS levels were associated with diffuse nodal hyperplasia of the zona fasciculata in the cortex. The results suggest that there may be a LRHD variant running with excessive DOCS secretion and related to pathogenetically related to hyperplasia of predominantly the zone fasciculata in the adrenal cortex.     

Foci of the rat mite Ornithonyssus bacoti (Mesostigmata, Macronyssidae) and rat-mite dermatitis in Moscow]

High density of the rat population in Moscow in 1990-1991 resulted in the appearance of Ornithonyssus bacoti foci and of cases of the rat-mite dermatitis in humans. A total of 36 foci of the disease were examined and eradicated. A method for the detection of such foci has been developed. Two types of foci are distinguished, communal and industrial, and their specific features as regards the rodent and mite populations and clinical features of dermatitis in humans are described. A system of measures for liquidation of foci of rat mites is suggested, including rat and mite eradication and treatment of the patients. Specific features of these measures for various types of foci and in case of a focus reappearance are enumerated.     

Ways of drug action on the restorative processes in the myocardium in experimental myocardial infarct]

On a model of experimental myocardial infarction there is demonstrated the stimulating effect of inosine (most distinctly) and also of stimulants of the nucleic acids synthesis and of retabolil on the formation of the post-infarction scar, the processes of compensatory hyperfunction and hypertrophy, all this finally speeding up the restoration of the myocardial function as a whole. At the root of this research carried out on 276 rabbits there lie histological, histochemical, electron microscopic, biochemical, electrographic findings and determination of the intracardiac hemodynamics.     

Mapping and molecular characterization of novel monoclonal antibodies to conformational epitopes on NH2 and COOH termini of mammalian tryptophanyl-tRNA synthetase reveal link of the epitopes to aggregation and Alzheimer's disease

Tryptophanyl-tRNA synthetase (TrpRS) is an interferon-induced phosphoprotein with autoantigenic and cytokine activities detected in addition to its canonical function in tRNA aminoacylation. The availability of monoclonal antibodies (mAbs) specific for TrpRS is important for development of tools for TrpRS monitoring. A molecular characterization of two mAbs raised in mice, using purified, enzymatically active bovine TrpRS as the inoculating antigen, is presented in this report. These IgG1 antibodies are specific for bovine, human and rabbit but not E. coli TrpRS. Immunoreactivity and specificity of mAbs were verified with purified recombinant hTrpRS expressed in E. coli and TrpRS-derived synthetic peptides. One of the mAbs, 9D7 is able to disaggregate fibrils formed by Ser32-Tyr50 TrpRS-peptide. Epitope mapping revealed that disaggregation ability correlates with binding of 9D7 to this peptide in ELISA and immunocytochemistry. This epitope covers a significant part of N-terminal extension that suggested to be proteolytically deleted in vivo from the full-length TrpRS whereas remaining COOH-fragment possesses a cytokine activity. For epitope mapping of mAb 6C10, the affinity selected phage-displayed peptides were used as a database for prediction of conformational discontinuous epitopes within hTrpRS crystal structure. Using computer algorithm, this epitope is attributed to COOH-terminal residues Asp409-Met425. In immunoblotting, the 6C10 mAb reacts preferably with (i) oligomer than monomer, and (ii) bound than free TrpRS forms. The hTrpRS expression was shown to correlate with growth rates of neuroblastoma and pancreatic cancer cells. Immunohistochemically both mAbs revealed extracellular plaque-like aggregates in hippocampus of Alzheimer's disease brain.     

Dynamics of lipid peroxidation in isoprenaline-induced myocardiopathy.

The dynamics of lipid peroxidation in isoprenaline-induced myocardiopathy was studied in rats. Spontaneous and Fe(II)- catalyzed generation of malondialdehyde (MDA)-like products and chemiluminescence in the heart, liver and brain homogenates were measured. The increase in the interval between treatment of rats with isoprenaline and their killing up to 48 hours led to an increase in MDA content in the heart. Both spontaneous and Fe(II)-induced chemiluminescence also reached their maxima after 48 hours. These data show that well expressed lipid peroxidation in the rat heart occurs approximately 48 hours after isoprenaline application. Isoprenaline metabolization in the liver leads to generation of activated oxygen species which are able to induce lipid peroxidation in the presence of Fe(II). The treatment of rats with isoprenaline caused well-expressed lipid peroxidation in the brain. The maximum of this process occurred approximately 36 hours after isoprenaline application. The results show that both spontaneous and Fe(II)-induced chemiluminescence might be used for the estimation of lipid peroxidation in rat heart homogenates.